Background.
Monoclonal gammopathy of unknown significance (MGUS) is a
potentially malignant condition associated with a cumulative
probability of progression into one of the malignant forms of
monoclonal gammopathy approximately 1% per year (Kyle et al., New
Engl J Med 2002). Aims. The aims of this study
were to verify the validity of already known risk factors
separating benign and malignant MGUS using Register of Monoclonal
Gammopathy (RMG) of Czech Myeloma Group. Methods.
Before inclusion to RMG all persons signed informed consent. Total
of, 1448 persons with MGUS were enrolled to the RMG in the Czech
Republic retrospectively and prospectively, from May 2007 to
November 2011. A total of 99,3% (1439/1448) persons were analyzed.
The median follow up was 5 years (range 1.0 to 18.0).
Results. Total of 7,1% (96/1356) persons with MGUS
progressed into malignant form; 75% (72/96) into multiple myeloma;
10,4% (10/96) into Waldenstrom macroglobulinemia; 5,2% (5/96) into
malignant lymphoma; 2,1% (2/96) into primary amyloidosis; 7,3%
(7/96) into other types of malignancy with the median time to
transformation 3 years (range 0-15 years). Variables associated
with significantly higher risk of transformation were as follows:
serum paraprotein levels >15 g/l (25,8% vs. 4,48%; p< 0.001),
bone marrow plasma cells infiltration >5% levels (22,3% vs.
5,4%; p< 0.001), abnormal κ/λ index < 0,26 or > 1,65
(75,6% vs. 42,7%; p< 0.001), serum baseline lactate
dehydrogenase levels >3,75 ukat/l, (7,82% vs. 4,62%; p= 0.016)
and serum baseline hemoglobin levels <120 g/l (7,82% vs. 4,62%;
p= 0.007). In contrast to stratification system published by
Rajkumar et al.(Blood 2005), we did not find any correlation
between Ig isotypes (non IgG vs. IgG) (32,6% vs. 29,5%; p= 0.523),
however high-risk subgroup (presence of all three abnormal risk
factors) belonged to a group with a relative risk (Hazard Ratio;
HR) almost 18 times higher than normal (17.54; CI (5.78; 53.22);
p<0,001) when Cox model was used to identify possible predictors
of malignant transformation. High HR (4.18, CI (2.59, 6.74), p
<0.001) also had a number of plasma cells greater than 5%
levels, serum paraprotein levels >15g /l (HR 3.64, CI (2.39,
5.54) p <0, 001) and pathological values of the κ/λ index HR was
2.9 (2.90 (1.47, 5.75), p = 0.002). Persons in the lowest risk
group had 5-year survival without malignant transformation in 96,7%
of cases with an annual risk of transformation under 1%, while the
highest risk group in 55,6% of cases with and annual risk of
transformation about 8-9%. Conclusions. Our
results confirm the validity of the known risk factors, except type
of Ig for prediction of MGUS transformation into malignancy.
Currently, we can well define the group with the lowest risk with
an annual risk of transformation < 1%. Further optimization of
the currently used model of stratification is required mainly for
other than low risk groups. At this point, our data form one of the
largest set of analyzed subjects with MGUS in the world; however, a
certain limitation is a short median follow-up.
Funding. Supported by grants: MSM0021622434 and
GAP304/10/1395